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Journal of Electrocardiology 52 (2019) 17–21
Contents lists available at ScienceDirect
Journal of Electrocardiology
journal homepage: www.jecgonline.com
Long–term prognostic significance of terminal QRS distortion
on patients with stemi and its correlation with the GRACE
scoring system
Ahmet Yılmaz, MD a,⁎, Kenan Demir, MD b, Recep Karataş, MD c, Mustafa Çelik, MD d, Ahmet Avcı, MD e,
Fikret Keleş, MD f, Ahmet Erseçgin, MD g, Nazif Aygül, MD b, Bülent Behlül Altunkeser, MD b
a
Karaman State Hospital, Cardiology Department, Turkey
b
Selçuk University, Faculty of Medicine, Cardiology Department, Turkey
c
Aksaray State Hospital, Cardiology Department, Turkey
d
Kirsehir Ahi Evran University, Faculty of Medicine, Cardiology Department, Turkey
e
Bursa Medical Park Hospital, Cardiology Department, Turkey
f
Elazig State Hospital, Cardiology Department, Turkey
g
Izmir Cigli State Hospital, Cardiology Department, Turkey
Introduction participating 247 centers in 30 countries. Greater than 70 years of
age, history of MI, higher Killip class, increased heart rate, low blood
The standard 12-lead electrocardiogram (ECG) continues to serve as pressure (BP), increased creatinine and cardiac biomarker levels
the most widely used tool in the diagnosis and risk stratification of pa- and ST segment deviation were found to be associated with increased
tients with acute ST-segment elevation myocardial infarction (STEMI) mortality rates. Data from this study were used to develop a
and several new ECG parameters have been shown to be useful in deter- scoring system, namely the GRACE scoring system, to estimate mortality
mining patients at higher risk [1–3]. rate in patients with ACS at 6 and 36 months [13,14]. This
Risk classification for mortality in patients with acute coronary syn- scoring system is recommended in many of the current ACS guidelines
drome (ACS) not only provides better management and follow-up, but [15].
also helps determine which patients are likely to benefit most from The association of G3I with long-term mortality and its
treatment [4]. correlation with the GRACE (version 2.0) risk score system has not yet
Terminal QRS distortion hypothesis, also referred to as been fully investigated. The aim of the current study is to investigate
Grade 3 ischemia (G3I), is a strong indicator of in-hospital short- the effect of G3I on in-hospital and long-term mortality in patients
term mortality and the success of reperfusion in patients with STEMI with STEMI.
[3,5].
Previous studies have shown that patients with G3I on admission
ECG have poor in-hospital prognosis, poor response to fibrinolytic Material and methods
therapy, high mortality after primary percutaneous treatment and
larger infarcts [6–10]. Additionally, it has also been shown that G3I is Study population
associated with high SYNTAX score and high no-reflow rates [11].
And also patients with G3I on admission ECG had worse left ventricular Patients older than 18 years who were diagnosed as STEMI in
function and were more likely to develop complications during the cardiology clinic of Selçuk University Faculty of Medicine between
percutaneous intervention. More frequent LAD involvement and more January 2011 and January 2014 and who were admitted to the
widespread tissue damage, may in part, account for some of these hospital within b24 h after the onset of symptoms were included in
results [12]. the study.
In the Global Registry of Acute Coronary Events (GRACE) trial, We used the European Society of Cardiology (ESC) guidelines to di-
Eagle and colleagues followed a total of 102,341 patients with ACS for agnose STEMI. We classified patients into two groups according to the
mortality for 10 years. These patients were registered in any of the presence or absence of G3I on the admission ECG and performed
intra- and inter-group comparisons.
We obtained written informed consent from each participant in ac-
cordance with the Helsinki Declaration Principles.
⁎ Corresponding author at: Karaman State Hospital, 70200 Karaman, Turkey. Patients who had had N24 h of onset of chest pain, an ECG
E-mail address: dr.ahmetyilmaz@gmail.com (A. Yılmaz). with left or right branch block, a history of previous MI or
https://doi.org/10.1016/j.jelectrocard.2018.10.095
0022-0736/© 2018 Elsevier Inc. All rights reserved.
18 A. Yılmaz et al. / Journal of Electrocardiology 52 (2019) 17–21
bypass operation, inverted T waves in leads with ST elevation, pace- but not the G3I criteria were classified as having grade 2 ischemia
maker rhythm or those with an ambiguous ECG were excluded from (G2I) (Fig. 2).
the study.
We investigated and documented risk factors for cardiovascular
Statistical analysis
events, including age, sex, family history of coronary artery disease
(CAD), current smoking status (defined as an adult who has smoked
We used the SPSS 17 (SPSS Inc., Chicago, IL, USA) software
at least 100 cigarettes in his or her lifetime, both previous and active),
for statistical analysis. We used the Chi-square test for the comparison
hypertension (HT), hyperlipidemia (HL) (defined as the patients
of categorical variables and Student's t-test and Mann Whitney U
who needs treatment according to 2016 ESC/EAS Guidelines for the
test for the comparison of continuous variables. We also
Managment of Dyslipidemias), and diabetes mellitus (DM). We
performed logistic regression analysis and Cox regression
also recorded pre-procedural medications and Killip class on admission.
analysis using the forward stepwise method. Specifically, we used
Additionally, all patients underwent an echocardiographic examination
the Mann Whitney - U test to analyze the relationship between
before discharge. We used the bi–plan modified Simpson method
G3I and gender, HT, HL, DM, smoking, medication, complete
to measure left ventricular ejection fraction (LVEF). Laboratory studies
atrioventricular (AV) block development, intra-aortic balloon
included measurement of routine biochemistry, lipid profile,
pump (IABP) need and death; Kruskal-Wallis test to analyze the
hemogram, creatine kinase (CK), creatine kinase-MB (CK-MB), and
relationship between G3I and MI localization; and finally the logistic
troponin I. Finally, we calculated the GRACE scores and 36th-month
regression analysis to assess factors know to be associated with mortal-
GRACE mortality percentages of each patient from GRACE 2.0
ity in patients with STEMI such as age, gender, time of arrival, Killip
calculator.
class, DM, LVEF, CAD history, renal failure, cardiogenic shock, MI
Long-term follow-up was done by hospital visits at 1, 3, 6, 12,
localizationand GRACE score. The results were evaluated in the 95% con-
24, 36 months. The patients who were lost to follow up called by
fidence interval and we accepted p-values of 0.05 or less as statistically
telephone and invited for control, missing ones excluded from the
significant.
study (n: 71). Cause of deaths learned from the hospital registries.
Patients whose cause of death could not be determined excluded from
the study (n: 9). Results
A total of 216 patients (mean age: 60.9 ± 14.2 years, range:
Electrocardiographic evaluation 25 to 89 years) were enrolled into the study. Patients admitted
to the hospital within mean 4.4 ± 2 h after the onset of symptoms.
We obtained ECG from all patients who presented with Of these 170 (78%) were men and 46 (22%) women. The
STEMI within the first 12 h of symptom onset using the Nicoh average age of male and female patients was 59.2 and 66.5,
Cohden Cardiofax 12-channel ECG device. We then divided respectively.
patients into two groups based on the grade of ischemia, as defined While 59.7% of the patients were diagnosed with inferior MI,
by Birnbaum et al. [3]. G3I was defined as: absence of an S wave 40.3% had anterior MI and overall 17.1% of the patients had a
below the TP-PR isoelectric line in ≥2 leads that usually have a terminal history of CAD. 31.4% of the patients received fibrinolytic therapy,
S configuration (leads V1 to V3), or ST J-point amplitude ≥50% of the R 61.1% underwent primary percutaneous intervention and 31.9%
wave amplitude measured from the TP-PR baseline in ≥2 all other received Gp IIb/IIIa antagonist (tirofiban). Eighty-seven (40.2%)
infarct-related leads (Fig. 1). Patients meeting the ST elevation criteria patients developed new heart failure, 15 (6.9%) needed IABP
Fig. 1. Inferolateral (with posterior wall) myocardial infarction with terminal QRS distortion (G3I+) (J points emerge at ≥50% of the R wave amplitude in leads II, III and aVF).A. Yılmaz et al. / Journal of Electrocardiology 52 (2019) 17–21 19
Fig. 2. Anteroseptal myocardial infarction without terminal QRS distortion (G3I−) (S wave persists in leads V1, V2 and V3).
support and nine (4.1%) required temporary cardiac pacemaker The number of patients who received fibrinolytic therapy, who
insertion due to complete AV block. Of all the deaths, 64.9% underwent primary PCI and who received Tirofiban infusion did not dif-
were due to cardiovascular events. Twenty-two (10.1%) patients fer between the groups (p = 0.55, p = 0.26, p = 1; respectively). The
died during hospitalization and 35 (18%) of the 194 discharged number of patients who required IABP insertion (12.9% vs. 2.4%; p b
patients died during the 36-month follow-up period, summing up 0.001) and the number of patients with new onset heart failure (53.7%
to a total death rate of 26.3% (n = 57) at 36-month follow-up. vs. 30%; p b 0.001,) however, was significantly higher in the G3I+
The mean GRACE risk score points of 216 patients on admission was group (both include heart failure with preserved LVEF and heart failure
120 ± 34. with reduced LVEF).
Patients were grouped as G3I+ (QRS distortion positive: 93 pa- G3I was present in 67 of 183 (36.6%) patients with Killip Class I, 18 of
tients; 43.0%) and G3I− (QRS distortion negative: 123 patients; 22 (81.8%) patients with Class II, 6 of 9 (66.6%) patients with Class III,
57.0%). There was no significant difference in the distribution of G3I be- and 2 of 2 (100%) patients with Class IV. The differences between the
tween male (n = 75: 44.1%) and female (n = 18: 39%) patients (p = groups were all significant (p b 0.001).
0.61). Similarly, groups were well matched with regards to conven- There was no significant difference between groups with regards
tional CAD risk factors including DM, HT, HL, family history of CAD to complete AV block development (Total 10 patients; 6 patients at
and smoking (Table 1). G3I− group, 4 patients at G3I+ group), the need for transient pace-
maker insertion, the need for additional percutaneous intervention,
and urgent coronary bypass surgery (p N 0.05). Inferior MI
localization was significantly higher in complete AV block development
(p b 0.05).
Troponin I (7.4 ± 0.9 ng/ml vs. 5.4 ± 0.7 ng/ml; p = 0.04), (normal
range is between: 0.02–0.06 ng/ml) and CKMB (58 ± 9 U/l vs. 32 ±
Table 1
5 U/l; p = 0.02), (normal range is between: 0–24 U/l) levels on admis-
Basic characteristics and laboratory results of the patients enrolled into the study.
sion were higher in the G3I+ group. GRACE scores and percentages
Basic Characteristics and Laboratory Results G3I+ G3I− p Value were highly correlated with the presence of G3I both at GRACE risk
(n: 93) (n: 123)
score (points) and 36-month death risk (%) analysis (133 ± 36 vs. 111
Age (years) 62 59 0.07 ± 29; p b 0.001 and 38% ± 30% vs. 23% ± 21%; p b 0.001, respectively)
Gender (male), n (%) 75 (80.6) 95 (77) 0.61 (Table 1).
DM, n (%) 15 (16.1) 26 (21.1) 0.38
HT, n (%) 44 (47.3) 49 (29.8) 0.33
Age, time from symptom onset to admission, cholesterol values and
Smoking, n (%) 66 (70.9) 85 (69.1) 0.88 36th month cholesterol values did not significantly differ between the
CAD history, n (%) 14 (15.0) 23 (18.6) 0.58 groups. The systolic (110 ± 25 vs. 122 ± 23, respectively; p b 0.001)
HL, n (%) 14 (15.0) 15 (12.1) 0.55 and diastolic (67 ± 15 vs. 74 ± 13, respectively; p b 0.001) blood pres-
Systolic BP (mm Hg) 110 ± 25 122 ± 23 b0.001
sures were significantly lower in patients at G3I+ group. Patients in the
Diastolic BP (mm Hg) 67 ± 15 74 ± 13 b0.001
MI localisation – anterior, n (%) 44 (47.3) 43 (34.9) 0.07 G3I+ group had higher creatinine (p = 0.01) and lower LVEF (p =
LVEF on admission (%) 41 ± 8 45 ± 9 0.30 0.01) on admission.
Creatinine, mg/dl 1.0 ± 0.31 0.9 ± 0.26 0.01
LDL-cholesterol, mg/dl 122 ± 37 126 ± 36 0.40
HDL-cholesterol, mg/dl 35.7 ± 9 35.4 ± 8 0.79
Triglyceride, mg/dl 166 ± 107 181 ± 109 0.42
CKMB, U/L 58 ± 9 32 ± 5 0.02 Table 2
Troponin I, ng/ml 7.4 ± 0.9 5.5 ± 0.7 0.04 Long term clinical outcomes of patients G3I+ and G3I−.
36th month Creatinine, mg/dl 0.95 ± 0.21 0.95 ± 0.29 0.99
Clinical Outcomes G3I+ G3I− p Value
36th month LDL-cholesterol, mg/dl 98 ± 38 107 ± 41 0.29
(n: 93) (n: 123)
36th month HDL-cholesterol, mg/dl 35.9 ± 8.1 36.8 ± 7.9 0.56
36th month triglyceride, mg/dl 177 ± 13 185 ± 13 0.71 Heart Failure, n (%) 50 (53.7) 37 (30.0) b0.001
GRACE risk score (points) 133 ± 36 111 ± 29 b0.001 Total mortality, n (%) 33 (35.4) 24 (19.5) 0.01
36-month GRACE mortality risk (%) 38 ± 30 23 ± 21 b0.001 In hospital mortality, n (%) 16 (17.2) 6 (4.8) b0.001
Cardiovascular mortality, n (%) 24 (72.7) 13 (51.4) b0.001
HDL: high density lipoprotein, LDL: low density lipoprotein.20 A. Yılmaz et al. / Journal of Electrocardiology 52 (2019) 17–21
modality. Among these, only advanced age was found to be
significantly and independently associated with the G3I
occurrence. We found that G3I could be used as a predictor of
in-hospital mortality and mortality at 36 months. We also observed a
high correlation between G3I and the GRACE score and 36-month
GRACE death risk percentages. This is one of the other remarkable
findings of our study.
Eight independent parameters were used to calculate the GRACE
risk score. These include age, heart rate, systolic BP, renal function
(serum creatinine level), congestive heart failure (Killip class/diuretic
usage), ST-segment deviation on admission ECG, cardiac arrest
at admission and elevated cardiac necrosis biomarkers (troponin).
When these eight parameters forming the GRACE risk score were
examined the association with the G3I+ and G3I− groups, it was
seen that the systolic BP was lower and the heart rate, creatine and
troponin levels were higher in the G3I+ group. The Killip class was
found to be significantly higher. The number of patients with cardiac
arrest on admission was higher in the G3I+ group. Age and the number
of patients with ST segment deviation on admission ECG (because all
Fig. 3. Kaplan- Meier curve (At 36 month, the G3I− group has 24 deaths and 99 surviving patients are STEMI) did not differ significantly between both groups
patients. The G3I+ group has 33 deaths and 60 surviving patients). (Table 3).
The Kaplan Meier curve demonstrated that G3I is a strong
prognostic indicator of mortality. Taken together, our results
demonstrate that QRS morphology may be used to identify patients
at high risk for in-hospital and long-term mortality. These patients
In-hospital mortality rate (17.2% vs 4.8%, respectively; p b 0.001) should be closely monitored to reduce mortality rates. We also found
and the overall mortality rate at 36-month follow-up (35.4% vs 19.5%; that QRS morphology was significantly correlated with cardiogenic
p = 0.01) was significantly higher in patients in the G3I+ group. shock and heart failure development but not with the length of hospital
When all deaths were examined, at G3I+ group, 24 of 33 (72.7%) deaths stays.
were cardiovascular death. At G3I− group, 13 of 24 (54.1%) deaths were The prognosis of STEMI is closely associated with early risk stratifica-
cardiovascular death (Table 2). Cardiovascular mortality was higher in tion. In our study, we found that G3I is related to 36-month mortality. In
the G3I+ group (p b 0.001). many studies, it has been shown that G3I is associated with high
Multiple logistic regression analysis revealed that only higher age SYNTAX score and high no-reflow rates [11,15]. In addition, Yang et al.
(p = 0.002) was independently associated with G3I. showed that patients with anterior MI and G3I had larger infarct areas
The Kaplan-Meier curve revealed that mortality rate remained [17].
higher in the G3I+ group throughout all time periods during follow- In a review that included studies performed by several independent
up (Fig. 3). groups in Israel, the United States, Spain, Italy, Scandinavia, Turkey,
Korea and Japan Birnbaum et al. showed that patients with G3I on ad-
Discussion mission ECG had larger infarct size, less myocardial salvage and poorer
clinical outcomes [5]. Our study supports that these results will be sim-
The occurrence of G3I has been shown to be independent of the du- ilar in long-term follow-ups.
ration of ischemia, and its prevalence in patients with STEMI ranges be- Buber and colleagues have shown that G3I could be one
tween 19% to 53% [2,8,9,16]. of the strongest independent predictors of the no-reflow and
The association of G3I and long-term mortality in STEMI patients re- post-thrombolytic rescue PCI ratios [18]. Weaver and colleagues
mains unclear and its correlation with the GRACE score system is not and Rommel and his colleagues also found that patients with
studied before. G3I had larger microvascular damage detected on cardiac
In the current study, we investigated the relationship between Magnetic Resonance Imaging studies [19,20]. In another cardiac
G3I and variables known to be associated with mortality in Magnetic Resonance Imaging study, Valle-Caballero and
STEMI such as age, DM, LVEF, time to treatment, previous MI story, colleagues found that G3I on pre-reperfusion ECG in two or more
Killip classification, renal failure, cardiogenic shock, and treatment leads is independently associated with larger myocardium at risk and
infarct size in the setting of primary angioplasty-reperfused anterior
STEMI [21].
Tanrıverdi et al., in a prospective study conducted on 316
STEMI patients, found that patients with G3I on admission ECG had
less benefit from fibrinolytic therapy as compared with those without
Table 3
Association with GRACE risk score parameters and G3I.
G3I [6].
The Thrombolysis in Myocardial Infarction 4 (TIMI 4) trial
Grace score parameters G3I+ G3I− p Value revealed that patients with G3I were older, had more anterior
(n: 93) (n: 123)
STEMI, less often pre-infarction angina and higher rates of mortality
Age (years) 62 ± 15 59 ± 14 0.07 than patients without G3I. The combined weighted endpoint of
Heart rate (bpm) 103 ± 28 88 ± 17 b0.001
death, re-infarction, heart failure, or LVEF was higher in patients with
Systolic BP (mm Hg) 110 ± 25 122 ± 23 b0.001
Creatinine (mg/dl) 1.0 ± 0.31 0.9 ± 0.26 0.01 G3I.
Heart failure, Killip ≥II, n (%) 26 (27.9) 7 (5.6) b0.001 Bigi et al. compared LVEF between patients with and without G3I
Troponin I (ng/ml) 7.4 ± 0.9 5.5 ± 0.7 0.04 and found that while there was no significant difference at discharge,
ST deviation on admission ECG (%) 100 100 1 LVEF was significantly lower in patients with G3I at 6-month follow-
Cardiac arrest on admission, n (%) 9 (9.6) 4 (3.2) b0.001
up [22].A. Yılmaz et al. / Journal of Electrocardiology 52 (2019) 17–21 21
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